Functional effects of heavy metal exposures on N6-methyladenosine (m6A) methylation and other Epitranscriptomic modifications in the central nervous system

Among different RNA methylations, N6-methyladenosine (m6A) is the most abundant in the brain and determines the fate of RNA through reversible processes using methyltransferases, demethylases, and methyl-binding proteins. The reversibility of m6A is an emerging regulatory mechanism for gene expression, regulating many aspects of RNA metabolism and influencing learning and memory processes. Global m6A profiles are dynamically modified via the activity of various writers, readers, and erasers. However, m6A alterations from exposure to heavy metals, including the metals lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) and the metalloid arsenic (As), and the impact on brain function, are not fully understood. This paper reviews recent work that may begin to shed light on how heavy metal exposures may affect m6A methylation and how this might impact central nervous system functioning.